研究內容 |
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[ 摘要 ]
幽門桿菌的感染已被證實與胃潰瘍、十二指腸潰瘍、胃癌等消化道疾病有關。
近年來研究顯示,除了細菌本身的因子外,宿主對臨床上幽門桿菌感染所產生的免疫反應逐漸受到重視。而基因多型性可能會直接影響該基因在轉錄、轉譯上的表達,間接影響一些免疫調控因子的表現而會影響免疫系統功能,進而影響疾病的嚴重程度。因此,本篇研究的目的在探討宿主基因多型性與幽門桿菌引起疾病之關聯性,實驗對象為台灣東部的原住民及非原住民族群。另外,本篇研究也探討在幽門桿菌感染有無的情況下,胃部黏膜組織human β-defensins的表達情形,以更深入了解宿主先天性免疫對幽門桿菌感染的反應。本實驗對象共納入191名幽門桿菌陽性病人(97名原住民與94名非原住民)與171名幽門桿菌陰性病人(90名原住民與81名非原住民),在實驗中利用Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)的方法判定ICAM-1 K469E與NOD1 E266K基因多型性的型別,另用reverse transcription- polymerase chain reaction (RT-PCR)以及免疫組織化學染色的方法分析human β-defensins在胃部黏膜組織的表達情形。
本篇研究的結果發現ICAM-1 K469E基因多型性的型別分布在原住民與非原住民族群中有顯著的差異(p<0.001)。另外在本實驗中也發現ICAM-1 K469E的K/K型別與NOD1 E266K的A/A型別可能是疾病產生的潛在危險因子。在human β-defensin的部分,我們發現在幽門桿菌陽性的病人胃黏膜組織中,human β-defensin 2的表現量明顯高於幽門桿菌陰性的病人(p<0.05)。
[ 英文摘要 ]
Helicobacter pylori infection is closely associated with gastroduodenal diseases. It has become apparent that not only the characteristics of the pathogen but also host genetics play an important role in determining susceptibility to and severity of infections. In this study, we evaluate the relationship between host genetic polymorphisms and disease outcome in H. pylori-infected aboriginal and nonaboriginal populations in eastern Taiwan. We also examine human β-defensins expression in gastric mucosal tissues with or without H. pylori infection for better understanding the innate immune response to H. pylori. In the experiment, 191 H. pylori-infected patients (97 aborigines and 94 nonaborigines) and 171 H. pylori-negative controls (90 aborigines and 81 nonaborigines) are enrolled in the study. Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis was performed for the K469E variant of the ICAM-I gene and the E266K variant of the NOD1 gene. We used reverse transcription- polymerase chain reaction and immunohistochemistry to examine human β-defensins expression in gastric mucosal tissues. In our results, there was a significant difference in ICAM-1 K469E polymorphism between aborigines and nonaborigines (p<0.001). In addition, KK genotype of ICAM-1 K469E polymorphism and AA genotype of NOD1 E266K polymorphism may be a potential risk factor in disease outcome. The mRNA expression of human β-defensin 2 in H. pylori-positive patients was significantly higher than that in H. pylori-negative patients (p<0.05). |